Simon Scheuring

Bio: Simon Scheuring is an academic researcher from Cornell University. The author has contributed to research in topics: Force spectroscopy & Membrane protein. The author has an hindex of 55, co-authored 154 publications receiving 8630 citations. Previous affiliations of Simon Scheuring include Curie Institute & French Institute of Health and Medical Research.

Cellular capsules as a tool for multicellular spheroid production and for investigating the mechanics of tumor progression in vitro

Abstract: Deciphering the multifactorial determinants of tumor progression requires standardized high-throughput preparation of 3D in vitro cellular assays. We present a simple microfluidic method based on the encapsulation and growth of cells inside permeable, elastic, hollow microspheres. We show that this approach enables mass production of size-controlled multicellular spheroids. Due to their geometry and elasticity, these microcapsules can uniquely serve as quantitative mechanical sensors to measure the pressure exerted by the expanding spheroid. By monitoring the growth of individual encapsulated spheroids after confluence, we dissect the dynamics of pressure buildup toward a steady-state value, consistent with the concept of homeostatic pressure. In turn, these confining conditions are observed to increase the cellular density and affect the cellular organization of the spheroid. Postconfluent spheroids exhibit a necrotic core cemented by a blend of extracellular material and surrounded by a rim of proliferating hypermotile cells. By performing invasion assays in a collagen matrix, we report that peripheral cells readily escape preconfined spheroids and cell–cell cohesivity is maintained for freely growing spheroids, suggesting that mechanical cues from the surrounding microenvironment may trigger cell invasion from a growing tumor. Overall, our technology offers a unique avenue to produce in vitro cell-based assays useful for developing new anticancer therapies and to investigate the interplay between mechanics and growth in tumor evolution.

Filming Biomolecular Processes by High-Speed Atomic Force Microscopy

Abstract: In the history of science and technology, researchers have always undertaken endeavors to enhance the degree of “directness of measurement”. With “directness of measurement”, we conceptualize that the essence of the object under investigation, the structure, dynamics, and function of biological samples in the scope of this Review, is entirely and straightforwardly assessed by the measurement, bypassing hypotheses and intricate data analysis. When the degree of measurement directness is low, conclusions derived from the gleaned data often differ depending on the formulation of hypotheses, analysis models, and the data interpretation. That is why conceptual consensus about a specific issue of the studied object is rarely reached based on indirect data. This is often the case for studies of structure–function relationship of proteins. Previously, scientists had to understand distinct qualities of proteins by measuring a sample containing a huge number of molecules. The results are ensemble-averaged quantities (often at equilibrium) that provide only limited information on the proteins of study. Proteins are dynamic in nature and work at the single-molecule level. Protein molecules fluctuate, undergo structural changes, bind to and dissociate from interaction partners, and traverse a range of energy and chemical states during molecular action. Most, if not all, of these dynamics and their statistical distributions are convoluted and hidden in ensemble averaging measurements. To overcome the limitations of ensemble measurements, single-molecule biophysics was developed more than two decades ago, with the use of fluorescence microscopy,1,2 optical spectroscopy,3,4 and optical and magnetic tweezers,5,6 whose performances were further improved by the advancements of improved optical microscopes, lasers, electronics, computers, and high-sensitivity video cameras and sensors. Using these techniques, our understanding of the functional mechanism of proteins has made significant steps forward. Moreover, super-resolution optical microscopy techniques bypassing the diffraction limit for fluorophore localization have recently been added to fluorescence microscopy.7−9 However, the degree of directness of measurement is still limited, because the protein molecules themselves are invisible in these single-molecule measurements. Protein structure is typically studied by X-ray crystallography, electron microscopy (EM), and nuclear magnetic resonance (NMR) spectroscopy. To date, these techniques have revealed detailed three-dimensional structures of over 94 000 proteins (Protein Data Bank (PDB), http://www.rcsb.org/pdb/home/home.do), with a growth rate of about 8000 novel structures per year (2010–2013). Yet, these techniques make use of ensemble averaging, and, more seriously, the obtained structures are merely limited to static snapshots of fixed conformations. Thus, the simultaneous and direct observation of structure, dynamics, and function of single protein molecules has long been infeasible, and hence the materialization of a technique allowing such an observation has long been awaited in biological sciences. An ideal microscopy technique that allows simultaneous observation of structure, dynamics, and function of single protein molecules has to meet all of the following conditions (see Table 1): (i) in-liquid specimen imaging, (ii) high spatial resolution, (iii) high temporal resolution, (iv) low invasiveness to the specimen, and (v) direct imaging of the specimen without the use of markers (in other words, resolving the structure of the specimen itself). Although efforts have been made to develop environmental electron microscopy techniques capable of observing unstained biological specimens in solutions,10 the strong electron dose that is required to achieve high contrast and spatial resolution instantaneously denatures the sample. Achieving the above-described goals by EM is a highly difficult, if not impossible, task. Conventional atomic force microscopy11 (AFM) meets most of the above-mentioned conditions, except for the third condition, that is, high temporal resolution, and the fourth condition, that is, low invasiveness, is only moderately satisfied. Table 1 Feasibility Comparison of Three Types of Microscopy

Chromatic Adaptation of Photosynthetic Membranes

Abstract: Many biological membranes adapt in response to environmental conditions We investigated how the composition and architecture of photosynthetic membranes of a bacterium change in response to light, using atomic force microscopy Despite large modifications in the membrane composition, the local environment of core complexes remained unaltered, whereas specialized paracrystalline light-harvesting antenna domains grew under low-light conditions Thus, the protein mixture in the membrane shows eutectic behavior and can be mimicked by a simple model Such structural adaptation ensures efficient photon capture under low-light conditions and prevents photodamage under high-light conditions

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

J-aggregates: from serendipitous discovery to supramolecular engineering of functional dye materials.

Abstract: J-aggregates are of significant interest for organic materials conceived by supramolecular approaches. Their discovery in the 1930s represents one of the most important milestones in dye chemistry as well as the germination of supramolecular chemistry. The intriguing optical properties of J-aggregates (in particular, very narrow red-shifted absorption bands with respect to those of the monomer and their ability to delocalize and migrate excitons) as well as their prospect for applications have motivated scientists to become involved in this field, and numerous contributions have been published. This Review provides an overview on the J-aggregates of a broad variety of dyes (including cyanines, porphyrins, phthalocyanines, and perylene bisimides) created by using supramolecular construction principles, and discusses their optical and photophysical properties as well as their potential applications. Thus, this Review is intended to be of interest to the supramolecular, photochemistry, and materials science communities.

Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches

Abstract: Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs.

Structural determinants of water permeation through aquaporin-1.

Abstract: Human red cell AQP1 is the first functionally defined member of the aquaporin family of membrane water channels. Here we describe an atomic model of AQP1 at 3.8A resolution from electron crystallographic data. Multiple highly conserved amino-acid residues stabilize the novel fold of AQP1. The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport, whereas the water selectivity is due to a constriction of the pore diameter to about 3 A over a span of one residue. The atomic model provides a possible molecular explanation to a longstanding puzzle in physiology-how membranes can be freely permeable to water but impermeable to protons.